Ginsenoside Rk2 Provides Multidimensional Relief for Ulcerative Colitis by Improving Intestinal Barrier Function, Reshaping Gut Microbiota, and Regulating Th17/Treg Balance.

Ulcerative colitis (UC) is a multifactorial inflammatory bowel disease associated with intestinal barrier integrity, gut microbiota, and immune homeostasis. According to previous studies, ginsenoside Rk2 (Rk2) demonstrated anti-inflammatory activity in cocultures of Caco-2 and THP-1 cells. This study was the first to demonstrate that Rk2 positively impacted UC by regulating the "barrier-microbiota-immune" axis. Rk2 not only improved inflammatory factor levels and colitis symptoms but also enhanced intestinal epithelial barrier function via increased transepithelial electrical resistance (TEER) values and elevated expressions of tight junction proteins, remodeled gut microbiota via enriching its diversity and composition and increasing short-chain fatty acids (SCFAs) levels, and maintained intestinal homeostasis via restoring Th17/Treg balance. Moreover, the influence of Rk2 on UC might be mediated via the TNFSF14/LTβR/NIK pathway. In summary, Rk2 exerted a beneficial effect on UC by providing multidimensional regulation and was a potential natural therapeutic agent for UC.